Masui Hideyuki, Kawada Kenji, Obama Kazutaka
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Department of Surgery, Hirakata Kohsai Hospital, Osaka 573-0153, Japan.
Int J Mol Sci. 2024 Dec 24;26(1):6. doi: 10.3390/ijms26010006.
Colorectal cancer (CRC) is often associated with metastasis and recurrence and is the leading cause of cancer-related mortality. In the progression of CRC, recent studies have highlighted the critical role of neutrophils, particularly tumor-associated neutrophils (TANs). TANs have both tumor-promoting and tumor-suppressing activities, contributing to metastasis, immunosuppression, angiogenesis, and epithelial-to-mesenchymal transition. Tumor-promoting TANs promote tumor growth by releasing proteases, reactive oxygen species, and cytokines, whereas tumor-suppressing TANs enhance immune responses by activating T cells and natural killer cells. Understanding the mechanisms underlying TAN mobilization, plasticity, and their role in the tumor microenvironment has revealed potential therapeutic targets. This review provides a comprehensive overview of TAN biology in CRC and discusses both the tumor-promoting and tumor-suppressing functions of neutrophils. Novel therapeutic approaches targeting TANs, such as chemokine receptor antagonists, aim to modulate neutrophil reprogramming and offer promising avenues for improving treatment outcomes of CRC.
结直肠癌（CRC）常与转移和复发相关，是癌症相关死亡的主要原因。在CRC的进展过程中，最近的研究突出了中性粒细胞，特别是肿瘤相关中性粒细胞（TANs）的关键作用。TANs具有促肿瘤和抑肿瘤活性，促进转移、免疫抑制、血管生成以及上皮-间质转化。促肿瘤TANs通过释放蛋白酶、活性氧和细胞因子促进肿瘤生长，而抑肿瘤TANs则通过激活T细胞和自然杀伤细胞增强免疫反应。了解TAN动员、可塑性及其在肿瘤微环境中的作用机制揭示了潜在的治疗靶点。本综述全面概述了CRC中TAN的生物学特性，并讨论了中性粒细胞的促肿瘤和抑肿瘤功能。针对TANs的新型治疗方法，如趋化因子受体拮抗剂，旨在调节中性粒细胞重编程，为改善CRC的治疗结果提供了有前景的途径。
